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Much effort has been devoted to the metabolic engineering of Klebsiella pneumoniae; however, our knowledge of the actual expression level of promoters used in K. pneumoniae is limited. In this study, the expression levels of three promoters were compared systematically by using the lacZ reporter gene with different carbon sources in K. pneumoniae. The results showed that, although promoters P T5 and P tac designed for Escherichia coli were functional, P T5 appeared more efficient and the induction/repression ratio of P tac was decreased extremely in K. pneumoniae. The basal level of P tac for lacZ expression reached 396.5 U/mg, which was 9.5-fold higher compared with P T5 in LB medium, indicating P tac can be used as an efficient 'constitutive' promoter as well as an efficient induced promoter in K. pneumoniae. In different carbon sources medium, a newly constructed endogenous constitutive P bud proved to be a stable and weak promoter. On the basis of our data, a set of P bud and P tac promoters could meet the broad range (about 1,000 orders of magnitude) of gene expression needed for engineered K. pneumoniae in glycerol-based medium. [ABSTRACT FROM AUTHOR]

Soil is a heterogeneous medium that exhibits considerable variability in both spatial and temporal dimensions. Proper management of field variability using variable-rate fertilization (VRF) techniques is essential to maximize crop input–output ratios and resource utilization. Implementing VRF technology on a localized scale is recommended to increase crop yield, decrease input costs, and reduce the negative impact on the surrounding environment. This study assessed the agronomic and environmental viability of implementing VRF during the cultivation of summer maize using an on-the-go detector of soil total nitrogen (STN) to detect STN content in the test fields. A spatial delineation approach was then applied to divide the experimental field into multiple management zones. The amount of fertilizer applied in each zone was determined based on the sensor-detected STN. The analysis of the final yield and economic benefits indicates that plots that adopted VRF treatments attained an average summer maize grain yield of 7275 kg ha−1, outperforming plots that employed uniform-rate fertilization (URF) treatments, which yielded 6713 kg ha−1. Through one-way ANOVA, the yield p values of the two fertilization methods were 6.406 × 10−15, 5.202 × 10−15, 2.497 × 10−15, and 3.199 × 10−15, respectively, indicating that the yield differences between the two fertilization methods were noticeable. This led to an average yield increase of 8.37% ha−1 and a gross profit margin of USD 153 ha−1. In plots in which VRF techniques are utilized, the average nitrogen (N) fertilizer application rate is 627 kg ha−1. In contrast, in plots employing URF methods, the N fertilizer application rate is 750 kg ha−1. The use of N fertilizer was reduced by 16.4%. As a result, there is a reduction in production costs of USD 37.5 ha−1, achieving increased yield while decreasing the amount of applied fertilizer. Moreover, in plots where the VRF method was applied, STN was balanced despite the reduced N application. This observation can be deduced from the variance in summer maize grain yield through various fertilization treatments in a comparative experiment. Future research endeavors should prioritize the resolution of particular constraints by incorporating supplementary soil data, such as phosphorus, potassium, organic matter, and other pertinent variables, to advance and optimize fertilization methodologies. [ABSTRACT FROM AUTHOR]

Background: The first-line agents comprising antihistamines for chronic urticaria, are not completely satisfactory. Tripterygium wilfordii Hook F (TwHF), a Chinese herb, has been developed into several Tripterygium agents and have definite effects on autoimmune and inflammatory diseases. In chronic urticaria, however, their values of practical application remain unclear. The aim of this study was to investigate the efficacy and safety of TwHF in patients with chronic urticaria. Methods: Several databases were systematically searched including PubMed, Embase, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure, Chinese Scientific Journals Database, Wan Fang Database, and Chinese Biomedicine. Randomized controlled trials comparing antihistamines with TwHF or Tripterygium agents in combination with antihistamines were included. Revman5.3 was utilized to calculate risk ratios (RR) with 95% confidence intervals (CI). This study was registered with PROSPERO, number CRD42018091595. Results: Twenty-one trials with 2565 participants were included in this analysis. Meta-analysis showed that, when antihistamines were combined with TwHF and Tripterygium agents, the curative effect in cases of chronic urticaria was superior to that of antihistamines alone (RR: 1.40; 95% CI: 1.33–1.46). The incidence rates of gastrointestinal disorder (RR: 2.91; 95% CI: 1.70–4.99) and menstrual disorder (RR: 6.00; 95% CI: 1.79–20.13) in drug combination groups were higher than those in controls, while other adverse events were similar between the two groups. After treatment, Dermatology Life Quality Index (RR: 1.23; 95% CI: 1.09–1.40), quality of sleep (RR: 1.50; 95% CI: 1.07–2.12), and daily activity (RR: 1.49; 95% CI: 1.25–1.78) were all improved. Furthermore, drug combination groups demonstrated less relapse (RR: 0.34; 95% CI: 0.25–0.45). Conclusions: TwHF and Tripterygium agents, in combination with antihistamines, appear to be more effective than antihistamines alone. Nevertheless, adverse events cannot be ignored. Large sample, multi-center, high-quality clinical studies are needed to verify the exact effects and safety of TwHF and Tripterygium agents in treatment of chronic urticaria. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death protein-1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have remarkable clinical efficacy in the treatment of non-small cell lung cancer (NSCLC); however, the breakdown of immune escape causes a variety of immune-related adverse events (irAEs). With the increasing use of PD-1/PD-L1 inhibitors alone or in combination with other therapies, awareness and management of irAEs have become more important. We aimed to assess the incidence and nature of irAEs associated with PD-1 and PD-L1 inhibitors for NSCLC.Methods: Articles from the MEDLINE, EMBASE, and Cochrane databases were searched through December 2017. The incidence of overall and organ-specific irAEs was investigated in all clinical trials with nivolumab, pembrolizumab, atezolimumab, durvalumab, and avelumab as single agents for treatment of NSCLC. We calculated the pooled incidence using R software with package Meta.Results: Sixteen trials were included in the meta-analysis: 10 trials with PD-1 inhibitors (3734 patients) and 6 trials with PD-L1 inhibitors (2474 patients). The overall incidence of irAEs was 22% (95% confidence interval [CI], 17-28) for all grades and 4% (95% CI, 2-6) for high-grade irAEs. The frequency of irAEs varied based on drug type and organ, and patients treated with PD-1 inhibitors had an increased rate of any grade and high-grade irAEs compared with patients who received PD-L1 inhibitors. Organ-specific irAEs were most frequently observed in, in decreasing order, the endocrine system, skin, pulmonary tract, and gastrointestinal tract. The total number of patients whose death was attributed to irAEs was 14 (0.34%), and most (79%) of these patients died because of pneumonitis. The median time to the onset of irAEs after the initiation of treatment was 10 weeks (interquartile range, 6-19.5 weeks) and varied depending on the organ system involved.Conclusions: The specificity of irAEs was closely associated with the mechanism of PD-1/PD-L1 antibodies involved in restarting anticancer immune attacks. Comprehensive understanding, timely detection, and effective management could improve the compliance of patients and guide the interruption of treatment. [ABSTRACT FROM AUTHOR]